Definitive studies on ribonulceotide reduction, which appears to be related to the control of DNA synthesis, are, at present, largely confined to microbial systems. The objective of this research is to study the mechanism of this reaction in mammalian cells. The activity of ribonucleotide reductase is increased in extracts of rapidly proliferating rabbit bone marrow, the source of enzyme for this study, both the rate of hematopoeisis and ribonucleotide reduction are increased. Two protein fractions, S1 and S2, seperated from partially purified preparations of the bone marrow enzyme must be recombined for activity. S1 and S2 will be highly purified and characterized with respect to molecular size. The catalytic and regulatory roles of S1 and S2 will be determined by the binding cofactors (such as B12 coenzyme and iron) as well as nucleotide substrates and effectors. The interaction of S1 and S2 with hydroxylurea, an antitumor agent which inhibits reductase activity will be examined. The substrate, the ablity of the enzyme to catalyze the reduction of all four ribonucleotide and a possible regulatory role of nucleoside triphosphates. The role of the thioredoxin-thioredoxin reductase as a hydrogen donor system in ribonucleotide reduction in bone marrow will also be investigated.